VITAMIN C and ALLERGY TREATMENT
Submitted to Medical Hypotheses February 1986
作者:Robert F. Cathcart, M.D.
虽然有五类明显的免疫球蛋白：IgG、IgA、IgD、IgE、IgM 抗体，免疫球蛋白结构的基本单位是由2 条相同的轻多肽链和2条相同的重多肽链通过二硫键（SS）连结在一起。这个基本单位的典型模式是使这些肽链排列为一个“Y”字形。2条重链形成一夹角，指向它们的中间，并被二硫键连在一起，以这样一种形式排列在一起，以形成Y“字的底部。这个底部，或Fc段，调节抗体对机体组织，包括免疫系统的各种细胞、一些巨噬细胞和补体的结合。连结在“Y”底部的双硫键在不同的抗体纲，甚至不同的亚纲的免疫球蛋白，各不相同。以IgE为例，5个基本单位在它们的底部连结起来。
Lewin (9)用生物化学方法分析了抗坏血酸在体内帮助二硫键还原的复杂情况：他推论：在体内环境下，当抗坏血酸供应充足时，抗坏血酸/脱氢抗坏血酸系统可以还原硫氢基/二硫化合物系统（如抗坏血酸能还原二硫键）。虽然Lewin 没有专门提到抗体的二硫键，他确提到DTT、胱氨酸、谷胱甘肽和肾上腺色素等等。
从Lewin 对体内多个代谢系统的分析，任何人均可获得如下印象：一些系统很可能是处于抗坏血酸/脱氢抗坏血酸的等式中，如果AA/DHA比值高，系统将会被还原，并带来有益的影响。我的临床经验已验证了这些印象。我和Lewin 不同之处仅是，在临床严重情况下，取得这些效果需要的抗坏血酸剂量是他预期的10~15倍。
因为Heisenberg 不确定法则（Heisenberg Uncertainty Principle），我认为这些推测很难验证，即使受最轻微的干扰，组织都不再正常和健康。虽然如此，出现在此的推测会解释一些关于免疫系统的临床观察报告。尤其是，这些推测会解释我的一些大剂量抗坏血酸对过敏性病变的作用的观察报告。
Submitted to Medical Hypotheses February 13, 1986.
I previously described that bowel tolerance (the amount that almost causes diarrhea) to oral ascorbic acid, increases in a person somewhat proportionally to the "toxicity" of his disease. Ascorbic acid ameliorates symptoms and sometimes cures certain diseases at high threshold levels near bowel tolerance. High concentrations of ascorbate cause the redox potential of the redox couple (ascorbate/dehydroascorbate, AA/DHA) to become reducing in diseased tissues. Allergic and sensitivity reactions are frequently ameliorated and sometimes completely blocked by massive doses of ascorbate. I now hypothesize that one mechanism in blocking of allergic symptoms is the reducing of the disulfide bonds between the chains in antibody molecules making their bonding antigen impossible. I further hypothesize that antibodies seek to match antigens only in areas where stray free radicals or a relatively oxidizing redox potential exists. The redox state of normal, healthy tissue does not allow for the bonding of antibodies to antigen. When antioxidant, free radical scavenging systems are overwhelmed, inflammatory, hypersensitivity, and "autoimmune" conditions may result.
Based on my experience with over 12,000 patients during the past 15 years, it has been my consistent observation that the amount of ascorbic acid dissolved in water which a patient, tolerant to ascorbic acid, can ingest orally without producing diarrhea, increases considerably somewhat proportionately with the "toxicity" of his illness (1,2). A person who can tolerate orally 10 to 15 grams of ascorbic acid in divided doses per 24 hours when well, might be able to tolerate 30 to 60 grams per 24 hours if he has a mild cold, 100 grams with a severe cold, 150 grams with influenza, and 200 grams per 24 hours with mononucleosis or viral pneumonia. Patients with hay fever, asthma, or environmental, drug, and food allergies and sensitivities usually tolerate from between 15 to 50 grams per 24 hours divided in 4 to 12 doses. Occasionally, tolerance is elevated even to higher amounts. There is frequently a dramatic decrease in symptoms just before diarrhea is produced. The individual patient has to be tolerant to oral ascorbic acid to achieve this effect but fully 80% of patients are tolerant enough. I call the process whereby the patient determines an appropriate dose of ascorbic acid, titrating_to_bowel_tolerance. Intravenous sodium ascorbate is even more effective.
I had previously hypothesized (3,4) that this ameliorating effect is largely due to the antioxidant, free radical scavenging effect of massive doses of ascorbate. Additionally, I had hypothesized that oxidants and free radicals formed in pathologic processes, oxidize ascorbate in the diseased tissues, exhausting the ascorbate first in the involved tissues, and then in the body more generally. There is then no vitamin C left over for known vitamin C functions first in the involved tissues, and then in the body more generally. I call this phenomenon acute_induced_scurvy. To the extent that free radicals are formed in allergic and sensitivity reactions, I think that these mechanisms apply. I have much clinical evidence that massive doses of ascorbate will ameliorate the secondary inflammatory cascades of injury and surgery.
I had hypothesized that the threshold where high doses of ascorbate suddenly became effective was where the ascor- bate/dehydroascorbate (AA/DHA) redox couple became reducing in the affected tissues (5). The dehydroascorbate formed, as ascorbate reduces free radicals and oxidizing substances, is not as toxic as the substances it reduced because the oxidizing redox potential of the dehydroascorbate is not as great as the oxidizing redox potential of the free radicals and oxidizing substances reduced. But additionally, if the amount of ascorbate ingested is enough to cause the AA/DHA redox couple to become reducing in the affected tissues, the dehydroascorbate formed will not be at all toxic. We should not just think of the ascorbate being a reducing substance and the dehydroascorbate being an oxidizing substance but should think of the redox potential of the redox couple, ascorbate/dehydroascorbate. I am able to negate any oxidizing effect of dehydroascorbate formed by making sure that the patient always ingests or is administered enough ascorbate to drive ascorbate into the depths of the diseased tissues in concentrations that exceed the dehydroascorbate formed. The redox potential of the redox couple is made reducing in the depths of the diseased tissues.
I have found that ascorbic acid in bowel tolerance doses is able to block many allergic reactions. I was alerted to this possibility when my own seasonal hay fever symptoms were blocked with 16 grams of ascorbic acid orally per 24 hours under conditions of moderate exposure to pollen. However, with exposure to higher doses of pollen, it required increased doses to maintain reasonable blockage of symptoms. Acute exposure to antigens could increased tolerance to 50 grams or more per 24 hours. When the exposure to allergens was very great, the blockage of symptoms was frequently incomplete. Experience with at least 1000 allergic patients has verified this finding in most cases. The limiting factor frequently seems to be the ability of the individual patient to consistently take that amount which almost causes diarrhea. The combination of ascorbate treatments with other treatments may result in even more optimum results.
Asthma attacks are frequently ameliorated similarly. When asthma is induced by exercise, massive doses taken before, during, and after the exercise will usually prevent otherwise expected attacks. Asthmatic attacks provoked by infections, especially upper respiratory infections, are most frequently prevented. The efficacy in these cases is mostly dependent upon the ability of the patient to tolerate sufficient doses of ascorbate. In severe acute situations, intravenous ascorbate may be especially effective in patients unable to take adequate amounts orally.
Urticaria, bee stings, poison oak, eczema, etc. can be ameliorated to varying degrees depending upon the tolerance of the patient to ascorbate and upon other as yet undefined variables. Ascorbate frequently works synergistically with other treatments for these allergic conditions.
Three patients with scarlet fever were treated who had the typical sandpaper like rash. The rash in these cases, the fever, and all other manifestations of the disease vanished in a few hours when the patients ingested bowel tolerance doses of ascorbic acid. The effect of ascorbate on scarlet fever and some food poisonings is so dramatic as to suggest a destruction of a finite amount of toxin which is not being replenished by the disease process.
About 2,000 patients were treated with penicillin, ampicillin, and cephalosporins in conjunction with bowel tolerance doses of ascorbate without any immediate allergic reactions to those medications. There was one delayed serum sickness-like reaction to penicillin in a young child. Her symptoms were temporarily lessened with large doses of ascorbate. It was most likely that she had not taken amounts of ascorbate sufficient to obtain the blocking effects being described here.
Several mononucleosis patients were inadvertently given penicillin along with ascorbic acid and had no allergic reactions. This experience is of note because of the very high incidence of allergic reactions to penicillin in patients with mononucleosis. One patient (having been given penicillin without ascorbate elsewhere) who presented with a typical allergic rash, had the rash disappear in minutes when given ascorbate intravenously.
As the protection of ascorbic acid against allergic reactions to certain antibiotics became increasingly more apparent, I expanded my indications for antibiotics somewhat. While the treatment of established Candida infections with ascorbate is complicated and of value only in conjunction with other treatments, women who have a tendency to vaginal yeast infections whenever given antibiotics, have a marked reduction of this complication when taking bowel tolerance doses of ascorbic acid along with the antibiotics. Additionally, ascorbate seems to act synergistically with antibiotics and significantly broaden the spectrum of activity of the antibiotics.
I have not as yet had a patient have an anaphylactic reaction to anything while taking large doses of ascorbate. The number of possibilities of anaphylactic reactions may have been so few as to make this observation of limited value. However, the spectrum of conditions which ascorbate ameliorates suggests that ascorbate should be taken along with any other indicated treatments whenever there is any danger of anaphylactic reaction.
The observation of Kalokerinos (6) that ascorbate prevents sudden infant death syndrome (SIDS) may or may not be relevant here but bears repeating whenever possible.
While vitamin C has been described as having an anti-histamine like effect (7,8), it is not strictly an antihistamine. Most antihistamines have an ethylamine moiety as is present in histamine but not ascorbate. Antihistamines appear to act by occupying "receptor sites" on effector cells and exclude the histamine; they are pharmacological antagonists. Vitamin C has no real stimulating effect on the central nervous system, as do most antihistamines at certain doses. The relief by ascorbate of malaise and some toxic effects on the brain and body in general, may be interpreted by a patient as somewhat stimulating however. Certainly ascorbate has no depressant effect on the CNS as do antihistamines. Vitamin C has no local anesthetic effect nor an atropine-like effect found with antihistamines. Ascorbate has no acute poisoning effect on the CNS no matter what dose is taken orally as do antihistamines.
Lewin described mechanisms whereby ascorbate assists in the formation of cyclic AMP (9) and cyclic AMP inhibits the release of histamine (10,11) from mast cells or basophils, but this is not an effect of antihistamines.
Therefore, ascorbate may be found to have some of the beneficial clinical effects which in a few instances might be similar to antihistamines, but ascorbate would often ameliorate a condition where an antihistamine had not helped. Additionally, ascorbate seems at times to work synergistically with antihistamines. Ascorbate is certainly not to be considered an antihistamine and has no similar pharmacological mechanism of action.
Food allergies, as those which produce classical IgE mediated symptoms such as urticarial rashes often respond rapidly. Bowel tolerance doses to the extent that they produce softened stools, even diarrhea, and decreased bowel transit time, reduce the duration of the reactions in addition to the blockage of the reactions.
Food sensitivities, or reactions not mediated by IgE frequently present more difficulties but bowel tolerance doses should be tried. Depending upon the underlying cause, one can expect in a significant percentage of patients that the intensity of reactions will be reduced and the duration of the reactions lessened.
Food poisoning and gastroenteritis may be dramatically relieved by massive doses of ascorbate. Experience is helpful in treating these conditions because the patients fear that ascorbic acid will intensify the diarrhea and other bowel discomfort. In an otherwise healthy bowel there is little difficulty. Doses of ascorbic acid far in excess of what would ordinarily be tolerated are administered. These doses do not usually add to the diarrhea but subtract from it. If one inadvertently overdoses greatly on the ascorbic acid, diarrhea will be produced, but there is relief of all of the other toxic symptoms and the diarrhea is benign, not usually associated with any pain.
While it is not always successful, I always test the effect of ascorbic acid on the food or chemical allergic patient. Bowel tolerance doses of ascorbic acid frequently have an ameliorating effect. However, the taking of the necessary doses of ascorbate is frequently difficult because of common nuisance problems in these patients. The production of much intestinal gas is frequent. Many patients with these allergies have a bowel flora that contains Candida albicans (12,13) and other gas producing organisms. Clinically, the sometimes enormous production of gas is suggestive that Candida and other organisms actually ferment ascorbate, or that ascorbate somehow accelerates their fermentation of other foods. However, some patients seem to break through a barrier where even larger doses of ascorbate reduce the amount of gas produced. Perhaps the decreased transit time associated with these large doses of ascorbic acid physically wash out much of the gas producing flora, or perhaps high enough levels of ascorbate finally inhibit fermentation. Interestingly, large amounts of intravenous sodium ascorbate in the range of 60 grams a day for a day or two, administered while the patient takes as much ascorbic acid as possible orally, may "prime" the patient in such a way that large doses of ascorbic acid are well tolerated by mouth. Measures to starve and kill intestinal Candida should be taken and when effective will reduce the intestinal gas.
Some of these patients will be allergic to certain vitamin C preparations. I find that by using the synthetic ascorbic acid fine crystals derived from corn syrup, the incidence of these reactions is reduced. Nevertheless, allergic symptoms will sometimes occur. Experience has shown that it is not the ascorbate itself which causes the allergic reaction but that some trace contaminant introduced in the manufacturing processes is responsible. When difficulties are encountered, other forms of ascorbate should be tried. Ascorbic acid made from sego palm, certain preparations labelled "natural", sometimes tablets or even timed-release forms may be better tolerated by individual patients. But these forms are more expensive and if used initially, may even more likely cause reactions. The most serious problem with certain alternative forms of ascorbic acid is that they may not have as beneficial an effect because blood levels of ascorbate reached are frequently not as high.
If mineral ascorbates are used, be mindful of the fact that it is the ascorbate part which is being discussed here and that the amount of mineral taken should be considered. Mineral ascorbates alter bowel tolerance in ways which have nothing to do with the mechanisms being discussed here. Calcium, magnesium, and potassium salts are sometimes used by allergic patients to block certain reactions and, when effective in an individual patient, may as well be used in the ascorbate form. This introduces a subject beyond the scope of this paper.
While it is not always successful, it is worth the effort to have every food allergic patient try to take bowel tolerance doses of ascorbic acid. If the bowel can tolerate it, tolerance doses may ameliorate symptoms of food and chemical allergy to varying degrees.
The definite effect of ascorbate on IgE mediated and other immunoglobulin mediated allergies has suggested to me a possible mode of action which can be understood in specific biochemical terms.
Although there are five distinct classes of human immunoglobulins, IgG, IgA, IgM, IgD, and IgE antibodies, the basic unit of immunoglobulin structure consists of two identical light polypeptide chains and two identical heavy polypeptide chains linked together by disulfide (SS) bonds. The classic model of this basic unit has these chains arranged in a "Y" shape. The two heavy chains have an angle (called the hinge) toward their middle and are linked together by SS bonds in such a way as to form together the base of the "Y". This base, or Fc fragment, mediates the binding of the antibody to host tissues, including various cells of the immune system, some phagocytic cells, and compliment. The SS bond linking in the base of the "Y" differs in different classes and even different subclasses of immunoglobulins. In the case of IgM, five of the basic units are joined together at their bases.
Each of the two light chains link to either side of the "V" of the "Y" shaped arrangement of the heavy chains, each by way of a single SS bond. Each of the two sides of the "V", made up of about half of a heavy chain and the whole of a light chain and bound together by the SS bond, are named Fab fragments. The upper ends of these Fab fragments are the specific antigen binding sites and are where antigens are bound.
Although the following analogy involves some inaccuracies, think of each Fab fragment of the "V" as being like a clothespin, the two wooden parts (part of one heavy chain and all of one light chain) being held together by a spring. The spring represents the SS bond. The far end of the wooden parts are called variable domains and are variously shaped so that they fit different antigens. When the pair of "clothespins" of an antibody find a match with an antigen, they hold onto that antigen.
In the IgE molecule there are 20 SS bonds. Sixteen are intrachain bonds. Two interchain SS bonds link the two heavy chains in the hinge region of the upper end of the Fc portion. One interchain SS bond links each of the two light chains to the adjacent heavy chains near the hinge. In vitro, by consecutive increases in the concentration of such reducing agents as dithiothreitol (DTT) and alkylation, one can sequentially disrupt the SS bonds (14). With a DTT concentration of 1 mM, the interchain SS bonds between the heavy and light chains are disrupted. These bonds are in the variable regions that bind antigen. Like taking the spring out of the clothespin, the antibody becomes unable to bind antigen. At a concentration of 2 mM of DTT, the SS bond within the heavy chains near the hinge are reduced and there is a marked decrease in the ability to attach to target cells (basophils and mast cells in the case of IgE). Higher concentrations of DTT cause more reduction and disruption of the IgE antibody.
Lewin (9), has analyzed biochemically the complex conditions favoring the reduction of disulfides by ascorbate in the human body. He concludes that under the conditions which exist in the human body, the ascorbate/dehydro- ascorbate system can reduce the thiol/disulfide system (i.e., ascorbate is capable of reducing SS bonds) when ascorbate is well supplied. Although Lewin did not specifically mention the SS bonds of antibodies, he did mention the dithiothreitol (DTT) (utilized in the experiment above), cystine, glutathione, and adrenochrome among others.
Symbolically, the reactions may be represented: AA = DHA + 2e + 2H+ -S-S- + 2H+ + 2e = 2-SH
One gains the impression from Lewin's analyses of several metabolic systems in the human body, that it is very possible that certain systems are in an equilibrium such that if the concentration of ascorbate to dehydroascorbate is high, the system will be reduced and usually favorably influenced. My clinical experiences have verified these impressions. I would differ with Lewin only in that I have found the magnitude of the doses necessary clinically to accomplish these feats are 10 to 15 times what he anticipated in serious disease states.
Clinically, allergic reactions are blocked by ascorbate somewhat to the degree that a threshold concentration of ascorbate might be being pushed into the affected tissues. The amount of ascorbate required seems somewhat proportional to the inflammation in the affected tissues. The threshold amount could be the amount of ascorbate necessary to reduce the free radicals and other oxidants present in the inflamed tissues, establish a relatively reducing redox potential in those tissues, and reduce the SS bonds of the antigen binding ends of the antibodies.
I hypothesize that an important effect of normal levels of vitamin C and other antioxidants is to reduce each of the interchain SS bonds of the two antigen binding ends of the antibody. The antigen binding ends are altered in such a way as they cannot bind anything. The pieces do not fly off in every direction but are held together, probably by Van der Waals forces, but still cannot bind anything.
Additionally, I hypothesize that this "unprimed" state is the usual state of antibodies in normal, healthy tissues. Antibodies are not "primed" to match antigens unless the antibodies wander into areas that have many free radicals or a relatively oxidized redox state. The problem in humans is that with surgery, injury, infection, allergic reaction, etc., the redox potential of affected tissues, because of free radicals and oxidants and the inability to make ascorbate, becomes less reducing too easily and antibodies become primed over an unnecessarily wide area and for too long a duration of time.
At first this unpriming effect might seem very undesirable under certain conditions but I think that ascorbate assists the body in modulating the antibody response toward an optimum. Certainly, the antibody response in hay fever, asthma, urticarial rashes, etc. does no good and that ascorbate should block these is desirable. An ideal situation would be that pollen, lying harmlessly on mucous membranes, would not be bound by antibodies because the antibodies would be unprimed, but that a bacteria or virus, etc. putting out toxins to ward off the immune system, would prime antibodies and cause antibodies to start seeking a match.
In my limited experience with ascorbate producing animals, I have noticed that in the cases of their surgery, injury, and infection, there is seemingly a shorter period of pain and disability than with humans. It is as if there were not the degree of secondary inflammatory cascade which is experienced by humans. This impression was verified by veterinarians. It was my impression dealing with many human injuries in a ski resort area that while acute pain immediately following an injury or surgery is not reduced, the pain the next day is reduced considerably when the patient is saturated with ascorbate. When an injury is totally immobilized or is not disturbed, it is common for there to be almost no pain at all in 24 hours. The lack of secondary inflammation is striking.
My experience with avulsed pieces of skin has been that when the piece was properly reapplied surgically, that if at the time of reimplantation the piece was viable, it would almost invariably survive. The dying of autogenous grafts caused by circulation being impaired due to secondary inflammation was virtually eliminated when large doses of ascorbate were taken.
In the case of infections, inflammation seems less in amount and duration in patients taking bowel tolerance doses of ascorbic acid. The inflammation seems more confined to the limited area directly involved in the infection. Nevertheless, most infections are shortened or aborted by ascorbate, seemingly by mechanisms mostly unrelated to inflammation. The theoretical value of reducing inflammation in treating many infections is attested to by the fact that physicians sometimes use steroids when treating infections, despite the fact that steroids seem to inhibit certain infection fighting mechanisms. In contrast, adequate doses of ascorbate seem to block inflammation to a more optimum degree while augmenting various infection fighting mechanisms.
I think that ascorbate, at the dose levels being discussed, manages to reduce the interchain SS bonds of antibodies except directly down on the tissues directly infected where the free radicals and oxidants are intensely concentrated. In the depths of infection, ascorbate assists the phagocytes maintain the respiratory burst killing of pathogens while protecting adjacent tissues from stray free radical damage (5).
Secondary inflammatory cascades are shut down by high doses of ascorbate scavenging free radicals, thereby preventing an unnecessarily wide area of relatively oxidized redox potential. Antibodies therefore remain unprimed, except in the small area most intensely directly affected by the injury or infection. The antibodies are prevented from unnecessarily matching antigens in what would have otherwise been large areas of secondary inflammation. Therefore the tendency toward autoimmune reactions is cut down considerably.
My hypothesis does not in anyway negate any of the elegant mechanisms of immunoregulation which have been worked out to explain necessary controls of the immune response but it adds a very effective control mechanism which markedly limits the area in which the more complex mechanisms must act.
Clinically, it is not uncommon to have a patient complain that an area of an old injury or old infection becomes symptomatic when he becomes ill subsequently with some other condition. Antibodies, formed by matching slightly altered self-molecules, slightly altered by the previous injury or infection, were at the time of the original insult suppressed as the original inflammation resolved. There have been described multiple mechanisms of immunoregulation in immunology texts whereby antibody reactions are brought under control (15). I hypothesize that an additional mechanism of suppression is that as the normal relatively reduced redox potential of the tissues is restored, the antibodies become reduced and unprimed. Subsequently, when the patient's free radical scavenging mechanisms are overwhelmed by some different condition, the redox potential in the body systemically becomes more oxidizing and old antibodies begin to seek matches. Some antibodies generated during the previous insult may then match those previously affected areas and result in pain and inflammation. Additionally, those antibodies may cross react with tissues similar to the previously affected tissues and more generalized conditions such as arthritis, myositis, tendonitis, neuritis, etc. may result. Foreign body molecules, especially from foods and chemicals, similarly may multiply antibodies which cross react with self-molecules. Ascorbate is frequently extremely effective in averting this situation because the systemic redox potential is kept relatively reducing despite local pathological processes generating considerable quantities of free radicals.
Sometimes fully developed autoimmune reactions can be markedly ameliorated by massive doses of ascorbate by driving reducing redox potentials directly into the depths of the autoimmune reactions. Quite frequently, if high levels of ascorbate are maintained such that the autoimmune response is mostly but not completely blocked, the reaction may become intermittent and reveal itself to be related to some previously unsuspected antigen and not be a true autoimmune reaction after all. In patients suspected of having food and chemical sensitivities, it may be difficult to determine by history which foods and chemicals are causing reactions because the reactions last for days. Frequently, the duration of these reactions are shortened by large doses of ascorbate sufficiently that the cause of the reactions become more obvious.
It is not uncommon to have a patient confused as to whether he is allergic to a certain substance or not because sometimes he seems to react to it and sometimes not. If, for instance, the patient has antibodies to certain milk proteins but he is otherwise under no stress, there are no inflammations going on, and the free radical scavengers of the body have a relatively reducing redox potential established in all tissues, then the patient will be able to drink some milk because all the antibodies will be in an unprimed state. But, if the free radical scavenging mechanisms have been overwhelmed systemically or locally in the gut exposed to the milk, the antibodies will be primed and will react if exposed to the milk antigen.
Free radical scavengers can be exhausted systemically by free radicals resulting from exposure to chemicals such as formaldehyde, chronic infections such as Epstein-Barr viral infections, other allergic reactions, injury, emotional stress, etc. resulting in priming of antibodies systemically. The more antibodies primed systemically, the more likely cross reactions will occur with self-molecules and autoimmune reactions occur.
Local reactions may exhaust free radical scavengers locally and prime antibodies. Particularly bothersome in this manner is Candida which is able to prime antibodies in the gut and lead to sensitivity reactions to the Candida itself and to many of the foods currently being eaten. Amoeba, Giardia and other intestinal pathogens may act similarly. As the inflammatory reactions become more intense and more free radicals are released, establishing more oxidizing redox potentials over wider areas, more antibodies are primed and sensitivities become more severe and more numerous. Inflamed mucous membranes are not as able to make appropriate digestive enzymes and therefore more macromolecules (e,g. undigested whole food proteins) would gain entrance into the body and be more likely to cause the production of matching antibodies.
Diseased mucous membranes and skin are more likely to admit antigens of all sorts including improperly digested macromolecules. Poor diet or overutilization of certain nutrients caused by stress, can result in digestive enzyme deficiencies from lack of nutrients necessary to make those enzymes. Poor diet and stress can also result in insufficient free radical scavengers to keep the redox potential sufficiently reduced to unprime antibodies. Junk foods can cause a patient to become allergic to good foods. Clinically. I have seen sugar ingestion cause hay fever attacks to pollen.
On the other hand, relief of exposure to antigen may allow the body to quiet inflammatory reactions, temporarily catch up with free radical scavenging, and allow for a temporary tolerance to an antigen because the antibodies are unprimed. For instance, a person with hay fever may, if put into an environment completely free of pollen for a period of time, subsequently be able to tolerate a moderate amount of pollen without immediately reacting because the antibodies in the nose had become unprimed. As a topical mild irritation starts in the nasal mucosa, a more oxidative redox potential is set up, the antibodies prime over a wider area and a more severe allergic reaction ensues. High doses of ascorbate can keep the area reduced to a greater degree and allow tolerance to higher exposure to pollen depending upon the concentration of ascorbate achieved in the mucous membranes. Sometimes when moderate doses of ascorbate are taken, there will be superficial irritations in the mucous membranes from pollen but the usual deep edema is averted.
Vigorous treatment of infections of the gut, such as Candida, Giardia, and other unfavorable intestinal pathogens, may reverse the relatively oxidizing redox potential and unprime the antibodies in the gut wall. Many times food and chemical sensitivities will be relieved if treatment is early enough. However, food sensitivities present for long periods may be more fixed. Nevertheless, massive doses of ascorbate, if taken in sufficient amounts, frequently add enough relief to make the result more satisfactory.
Pneumocystis carinii pneumonia (PCP), the most common immediate cause of death in AIDS patients, is particularly effectively treated with a combination of ascorbate and sulfa drugs. Of the complications of AIDS, PCP is the most easily treated with ascorbate. The responsiveness of PCP is because of the principles being discussed here.
The profound debility, fatigue, malaise, weight loss, etc., typical of PCP must be from acute induced scurvy because of the rapidity with which the condition responds specifically to ascorbate taken in high doses. Additional- ly, a major problem in PCP patients is that the incidence of allergic reactions to the indicated sulfa drugs is so high as to ultimately prevent their use in a high percentage of patients. The experimental drug, pentamidine, which causes many unfavorable reactions itself, is used partly as a result of this high incidence of allergic reaction to sulfa drugs and partly because some PCP cases seem not to respond favorably to the sulfa drugs.
Clinically, ascorbate blocks the allergic reactions to the sulfa drugs probably because of the mechanisms being discussed here. Additionally, ascorbate seems to works synergistically with sulfa drugs in the treatment of PCP. Usually it is possible to treat the patient who has a tendency toward PCP with ascorbate alone. Ascorbate, in combination with the rest of the AIDS protocol (3,4), will prevent the majority of attacks of acute PCP. The common cold and other respiratory diseases which predispose to the development of PCP can usually be prevented or treated with ascorbate. Occasionally, treatment with intravenous ascorbate is indicated if a respiratory viral disease is very severe. A patient with an actual attack of PCP can usually be treated as an outpatient, if caught early, with bowel tolerance doses of ascorbate plus the appropriate sulfa drug without difficulty and with very little probability of allergic reaction to the sulfa drug.
I think that the reason this combination is so successful is that the ascorbate prevents the acute induced scurvy, part of which is the creation of a relatively oxidative redox potential systemically which primes the antibodies. When ascorbate is used in adequate doses the priming of the antibodies is confined to an optimum small area directly about the primary site of the disease. The widespread priming of antibodies which increases enormously the probability of allergic reactions is mostly averted. If antibodies are formed to the sulfa drug in the primary site of the disease, those antibodies are in a unprimed state when circulating through the skin and cannot cross react with the skin and cause a skin rash.
Antibodies are secreted by the B cells (15). Each B cell produces antibodies which match a single antigen. There are elaborate methods whereby antigen is presented to the B-cell receptors by antigen-presenting cells with the help of T-helper cells. The B cells are stimulated to differentiate and divide into antibody forming cells which secrete the antibodies.
I think that if all the digestive enzymes are functioning properly and if the skin and mucous membranes are intact not allowing pathogens and other foreign macromolecules inside the body, not much antigen will be presented to the B cells. With inflammation damaging those membranes, more antigens will leak into the body and more antibodies will be produced. Ascorbate would lessen the area of secondary inflammation and thereby reduce the amount of antigen presented to the B cells and therefore reduce the amount of antibodies formed.
Additionally, it may be that the B-cell receptors (being identical to the antibodies) on the surface of the B cells are also reduced in tissues with relatively reduced redox potential and the formation of antibodies lessened for that reason.
T cell receptors have a structure similar to antibodies. The T cell receptor is made up of two polypetide chains, an alpha chain and a beta chain, which are, similarly to the antibodies, joined by a single disulfide bond (16). I hypothesize that this SS bond will be reduced and the T cell receptor site will be in an unprimed state when existing in normal tissues where there is a relatively reduced redox state. The receptor site would become primed when encountering free radicals or an area of relatively oxidized redox state. This mechanism would provide a similar restraint on cellular immunity cross reactions as with those of humoral immunity. To the extent this mechanisms unprimed cytotoxic T cells, it would restrict cellular immunity. To the extent it unprimed helper T cells, it would also (along with unpriming antibodies and B cells) limit humoral immunity.
The late Dr. Irwin Stone pointed out that most animals have the ability to make ascorbate. The higher primates lost the ability to make ascorbate about 65 million years ago. This inability to make ascorbate came about because of the loss of the liver enzyme l-gulonolactone oxidase which is necessary for the last step in making ascorbate from glucose (17).
Levine speculated that in emergency stress such as fighting for its life, an ascorbate making animal might utilize over 50 grams of glucose per hour in order to make 50 grams of ascorbate. This drain on blood glucose levels and resulting fluctuating levels of blood sugar, might impair its ability to fight (18). Additionally, I would add that there is an advantage to an animal in not utilizing glucose for the production of large amounts of ascorbate in that it could go longer without food without starvation.
But, perhaps more importantly, animals living on the ground who nose around in their own and other animals' wastes and eat dead and partially rotting foods, need the extra protection of detoxification afforded by the ascorbate free radical scavenging system. This ascorbate system is probably the reason a dog can bury a bone and let it rot for a few days and then dig it up and eat it without any difficulties. Up in the trees, wastes and dead things drop to the ground. The higher primates probably became relatively picky about what they ate, and living in sparse populations in the trees, had less to worry about from infectious diseases. The history of mankind indicates that as humans came out of the trees and lived together in large groups that infectious disease became more of a problem. Smallpox, cholera, plague, typhoid fever, typhus, etc. would regularly kill large percentages of the population of humans in large areas. Only with the advent of modern sanitation and medical science has there been a decrease in the deaths. AIDS is perhaps a disease which results from laxity of certain sanitation principles necessary in humans because of their lack of ability to make ascorbate.
Whatever the reason, higher primates lost their ability to make ascorbate. They probably could not have survived unless there had been some compensatory mechanisms available to make up for the lack of the ascorbate mechanism such as the enzymatic free radical scavengers, superoxide dismutase, catalase, glutathione, etc. A very complex immune system had been evolved in mammals who lived on the ground which was more than adequate for survival in the trees.
The evolutionary process fine tuned the immune system for hundreds of millions of years in animals who were able to make ascorbate. The mere 65 million years of evolution of the nonascorbate making primates has not completely solved a moderate hypersensitivity tendency in those primates. Perhaps one of the results of the big brain of homo sapiens will be that he will be able to acquire some of the advantages of the ascorbate making mechanisms without losing the advantage of not utilizing glucose for making ascorbate in a crisis and also not losing the advantages of the compensatory enzymatic free radical scavenging mechanisms.
It should be noted that when an organism which is not able to produce free radicals enters a host, the host's cellular immune systems can directly phagocytize that organism. If the organism has the ability to make enough free radicals to suppress cellular immune mechanisms, then antibodies of humoral immunity come to the rescue. Where cellular immunity is suppressed by free radicals, the antibodies are primed by those same free radicals. Where cellular immunity can accomplish its assigned task, antibodies need not become overly involved. Ascorbate assists cellular immune mechanisms and makes less likely the overproduction of antibodies and the risk of autoimmune reactions.
I suspect that these hypotheses will be difficult to prove because of the Heisenberg Uncertainty Principle. Even with the slightest disturbance, tissues are no longer normal and healthy. Nevertheless, such hypotheses as presented here would explain some clinical observations about the immune system. Particularly, these hypotheses would explain some of my observations of the actions of large doses of ascorbate in allergic conditions.
I hypothesize that a relatively reduced redox state normally exists in healthy tissues and that the disulfide bonds between the long and short chains of antibodies are reduced to thiols under these circumstances. The antibodies in this state are unprimed and unable to match antigens. This situation would apply whether the immunoglobulin existed in intra or extravascular pools, mucous secretions, on the surface membranes of B lymphocytes, basophils or mast cells. I hypothesize that a similar situation exists with T cell receptor sites. When the antibodies come into areas of the body where free radicals or an oxidizing redox potential exist, the antibody becomes primed and seeks antigen matches. This mechanism limits the area and time where antibodies may cross react with self-molecules and therefore reduces the probability of autoimmune disease. It is hypothesized that where this mechanism fails, a state of hypersensitization comes to exist despite other immunoregu- latory mechanisms. It is hypothesized that in fact, certain pathological conditions overwhelm free radical scavenging mechanisms in the human body and cause this state of hypersensitization to come to exist. Large doses of ascorbate can restore the relatively reduced redox state and disarm the antibodies systemically limiting the antigen seeking of antibodies to the primary areas of disease. Ascorbate producing animals do this naturally.
This mechanism provides an effective means where widespread secondary inflammatory cascades can be prevented. The morbidity from injury, surgery, allergy, tumors, and infection is reduced.
Rinse ascorbic acid and carbonated ascorbates off the teeth as prolonged exposure may cause damage to the enamel. Do not stop large doses of ascorbate suddenly when large doses have been taken for some time; especially do not stop it in a crisis situation.
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Content (C) 1995 and prior years, Robert F. Cathcart MD.